This proposal examines the hypothesis that a majority of aqueous outflow resistance is due to an accumulation of macromolecules in the extracellular spaces of the juxtacanalicular connective tissue and further, that certain components of this resistance- causing material are contained in aqueous humor. We anticipate that confirmation of these hypothesis will identify factors which lead to elevated intraocular pressure and glaucoma. Our group found that macromolecules present in aqueous humor dramatically affect the resistance to flow through microporous filters with pore dimensions similar to those of the juxtacanalicular meshwork. These macromolecules interact hypdophobically with the microporous filters and it is postulated that a similar interaction may occur in the juxtancanalicular connective tissue. The distribution of these macromolecules in the aqueous outflow system will be determine morphologically. A model is being developed that both theoretically and experimentally characterizes the permeability of the extracellular matrix gel that presumably fills the open spaces of the juxtacanalicular connective tissue. This model will be used to analyze the causes of primary open-angle glaucoma and pigmentary glaucoma.